The objectives of the Arizona SCOR are to determine the pathogeneses, natural histories, methods of early detection, and means of prevention of airways obstructive diseases (AOD). Eight closely related epidemiological, clinical, pathophysiologic, and experimental Projects, supported by six Cores, comprise a coordinated multidisciplinary program. Our ongoing longitudinal study of a general population sample including greater than 1650 households and greater than 4000 subjects will be continued to determine the overall evolution of AOD, to identify hosts factors and extrinsic risk factors for these diseases (including the interaction of immunological factors and bronchial irritants), and to evaluate methods for their early detection. New analyses are focused on the evolution of lung function over time, on the incidence of new disease, on the effects of changes in risk factors, and on detailed characterization of end point cases. An already enrolled and characterized population of greater than 1200 newborns will also continue to be followed in regard to the risk factors for and the consequences of lower respiratory tract illness in infancy. Extensive physiological and immunological studies of both enrolled children and their families are being carried when the children reach five years of age, allowing assessment of the effects of familial factors in both the children and their parents. Bronchial reactivity tests are included in these evaluations and in a new prospective study of middle aged males who are at the highest risk of developing new AOD. The methods necessary for evaluation of functional characteristics of infants and young children are being developed within the SCOR. To determine the acute immunologic changes induced by lower respiratory tract infections in infancy, a study of infants hospitalized with viral bronchiolitis is proposed, which the mechanisms of these acute changes and of their sequelae are being studied in a controlled animal model of viral bronchiolitis. The inheritance of bronchial hyperreactivity and the mechanisms underlying such hyperreactivity are being investigated in a rabbit model, and the apparently unique muscarinic receptors involved in regulating bronchomotor tone are being further investigated in the final project of the SCOR. Thus, the total program approaches the problem of AOD in a variety of complementary ways which bring together the expertise of many scientific disciplines.